Mild Prenatal Stress-Modulated Behavior and Neuronal Spine Density without Affecting Amphetamine Sensitization

Abstract

The present study investigated the effect of prenatal stress (PS) on juvenile behavior and adult amphetamine (AMPH) sensitization, as well as the effect of the interaction between experience (i.e. PS) and drug (i.e. AMPH) on cortical thickness and neuronal morphology in corticolimbic regions in rats. Juvenile male and female rats, exposed to gestational stress, were tested in behavioral tasks that included open field locomotion, elevated plus maze, novel object recognition, and play fighting behavior. The development and persistence of drug-induced behavioral sensitization in adults were tested by chronic AMPH administration and challenge, respectively. Spine density in corticolimbic regions was examined for structural plasticity. The findings showed that PS produced anxiety-like behavior in males. Furthermore, PS in males resulted in female-like play and enhanced partial rotation defense, whereas in females PS increased the probability of evasion in response to an attack. AMPH administration resulted in gradual increase in behavioral sensitization that persisted at least for 2 weeks; however, PS did not influence AMPH-induced behavioral sensitization in either male or female rats. Moreover, PS increased the spine density in the nucleus accumbens (NAc) and decreased it in the medial prefrontal cortex (mPFC) without any alteration in the orbital frontal cortex (OFC). Similarly, AMPH administration increased spine density in the NAc and mPFC, whereas a decrease was observed in the OFC. However, PS prevented the drug-induced alterations in the spine density observed in controls. In sum, PS modulated juvenile behavior and altered brain morphology without influencing AMPH-induced behavioral sensitization substantially.

Experience and the developing prefrontal cortex

“…In contrast, Mychasiuk et al (41) found an increase in spine density in both mPFC and OFC when animals were exposed to mild stress from embryonic days 12-16 (E12-E16) and the brains were examined at weaning. Using the same stress paradigm, Muhammad and Kolb (42) found a decrease in spine density in mPFC and no effect in OFC when the brains were examined in adulthood. Finally, Murmu et al (43) reported that moderate prenatal stress from E16-E21 resulted in decreased spine density and dendritic length in both the mPFC and OFC of adult degus.…”

“…We have subsequently shown that a variety of early experiences alter rat play behavior, including prenatal stress and preor postnatal tactile stimulation (42,60); in each case, there are changes in prefrontal development. There may be an important lesson here when we consider conditions in which human childhood play is not normal, such as in autism or ADHD.…”

Preconception paternal stress in rats alters dendritic morphology and connectivity in the brain of developing male and female offspring

“…When Muhammad and Kolb (2011a) looked at the brains of adult rats who had experienced gestational stress, they found a different pattern of changes: there was decreased spine density in mPFC and OFC, a result also seen in adult degus stressed gestationally (Murmu et al, 2006 Muhammad and Kolb (2011c) reported that adult rats who experienced infant maternal separation showed increased spine density in both mPFC and OFC.…”

Gender- and anxiety level-dependent effects of perinatal stress exposure on medial prefrontal cortex

“…In these areas, dynamic alterations in spine density have been reported, even after mild stress exposure between embryonic days 12-16 (Murmu et al, 2006). Prenatal stress experience increases spine density in the nucleus accumbens (NAc), whereas decreases it in the medial prefrontal cortex (mPFC) without any alteration in the orbital frontal cortex (OFC) of juvenile rats (Muhammad and Kolb, 2011b). On the other hand, male and female rats, separated daily for 3 h from the dam during postnatal day 3-21, display increased spine density in the NAc, the mPFC, and the OFC at periadolescent ages (Muhammad and Kolb, 2011a).…”